TY - JOUR
T1 - Cdk Inhibitor p27Kip1 and Hormone Dependence in Breast Cancer
AU - Arteaga, Carlos L.
AU - Medina, Daniel
AU - Brown, Myles
AU - Santer, Richard
PY - 2004/1/28
Y1 - 2004/1/28
N2 - p27Kip1 is an important regulator of the G1 to S transition. While a potent inhibitor of cyclin-dependent-kinase (Cdk)2, p27 is also involved in assembly of cyclin D/Cdk4 complexes. Although rarely mutated, p27 is functionally downregulated in many human cancers by mechanisms involving enhanced degradation, cytoplasmic mislocalization, and/or sequestration by cyclin D/Cdk complexes in response to oncogenic signals. Therefore, low levels and/or cytoplasmic localized p27 have been associated with enhanced malignancy and poor patient prognosis in many neoplasias including breast cancer. Recent data discussed below suggest that a threshold of p27 is required for response to antiestrogens and, conversely, that low levels predict for antiestrogen resistance. These results imply that hormone receptor-positive tumors with low and/or cytosolic p27 respond poorly to antiestrogens and should be considered for alternative therapeutic strategies.
AB - p27Kip1 is an important regulator of the G1 to S transition. While a potent inhibitor of cyclin-dependent-kinase (Cdk)2, p27 is also involved in assembly of cyclin D/Cdk4 complexes. Although rarely mutated, p27 is functionally downregulated in many human cancers by mechanisms involving enhanced degradation, cytoplasmic mislocalization, and/or sequestration by cyclin D/Cdk complexes in response to oncogenic signals. Therefore, low levels and/or cytoplasmic localized p27 have been associated with enhanced malignancy and poor patient prognosis in many neoplasias including breast cancer. Recent data discussed below suggest that a threshold of p27 is required for response to antiestrogens and, conversely, that low levels predict for antiestrogen resistance. These results imply that hormone receptor-positive tumors with low and/or cytosolic p27 respond poorly to antiestrogens and should be considered for alternative therapeutic strategies.
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U2 - 10.1158/1078-0432.CCR-031204
DO - 10.1158/1078-0432.CCR-031204
M3 - Article
C2 - 14734493
AN - SCOPUS:1442357323
SN - 1078-0432
VL - 10
SP - 368s-371s
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1 II
ER -